Funda Meric-Bernstam, MD, chair, the Department of Investigational Cancer Therapeutics–the Phase I Program, medical director, the Institute for Personalized Cancer Therapy (IPCT), the Nellie B. Connally Chair in Breast Cancer, the University of Texas MD Anderson Cancer Center, discusses results from the phase 2 DESTINY-PanTumor02 trial (NCT04482309) of fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) in patients with HER2-expressing solid tumors.

The open-label, multicenter study evaluated the efficacy of T-DXd in patients with advanced HER2-expressing solid tumors who were ineligible for curative therapy following progression on one or more systemic therapies. Tumor types included endometrial cancer, cervical cancer, ovarian cancer, biliary tract cancer, pancreatic cancer, and bladder cancer. A total of 267 patients received T-DXd at a dose level of 5.4 mg/kg every 3 weeks.

In the overall population, T-DXd elicited an overall objective response rate (ORR) of 37.1%, with a median duration of response (DOR) of 11.3 months, Meric-Bernstam reports. The median progression-free survival (PFS) was 6.9 months, and the median overall survival (OS) was 13.4 months. Further efficacy analysis according to immunohistochemistry (IHC) expression level showed that patients with IHC 3+ tumors experienced an ORR of 61.3%, a median duration of response (DOR) of 22.1 months, a median PFS of 11.9 months, and a median OS of 21.1 months, Meric-Bernstam adds. Comparatively, patients with IHC 2+ expression had an ORR of 27.2%, median DOR of 9.8 months, median PFS of 5.4 months, and a median OS of 12.2 months. Notably, clinically meaningful response rates were seen with the agent across all tumor types.

These findings highlight the potential of T-DXd to serve as a tumor-agnostic treatment for HER2-expressing malignancies, and offer a new therapeutic option for patients who have progressed after previous systemic treatments, Meric-Bernstam concludes.

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Funda Meric-Bernstam, MD, discusses results from the phase 2 DESTINY-PanTumor02 trial of fam-trastuzumab deruxtecan-nxki in HER2-expressing solid tumors.

Dr Meric-Bernstam on the Efficacy of T-DXd in HER2-Expressing Solid Tumors

Funda Meric-Bernstam, MD, chair, the Department of Investigational Cancer Therapeutics–the Phase I Program, medical director, the Institute for Personalized Cancer Therapy (IPCT), the Nellie B. Connally Chair in Breast Cancer, the University of Texas MD Anderson Cancer Center, discusses a first-in-human phase 1/2 study (NCT04902872) of CBX-12 in patients with advanced or metastatic solid tumors.

At the 2023 ASCO Annual Meeting, investigators presented data from the study evaluating the peptide drug conjugate, revealing that the maximum tolerated dose for the agent was found to be 45 mg/m2 for 3 days in a 21-day cycle or 60mg/m2 weekly. Myelosuppression was found to be the primary dose-limiting toxicity (DLT), although DLTs of febrile neutropenia and sepsis were both reported twice.

Notably, 5 patients experienced durable objective response or near objective responses per RECIST v1.1 criteria.

Notable any-grade adverse effects (AEs) included anemia (51.1%), fatigue (40.0%), and neutropenia (40.0%), which was not surprising based on the expected toxicity profile for this class of drugs, Meric-Bernstam says. Other any-grade AEs reported in more than 10% of patients included leukopenia, nausea, diarrhea, thrombocytopenia, vomiting, dehydration, and increased alanine transaminase.

The final recommended dosing schedule for CBX-12 in future studies has yet to be determined, Meric-Bernstam continues. However, investigators have been encouraged by the preliminary signs of efficacy displayed with the agent in this heavily pretreated patient population, Meric-Bernstam concludes.

Funda Meric-Bernstam, MD, discusses a first-in-human phase 1/2 study of CBX-12 in patients with advanced or metastatic solid tumors.


Dr Meric-Bernstam on the Investigation of CBX-12 in Advanced or Metastatic Solid Tumors

Funda Meric-Bernstam, MD, chair, the Department of Investigational Cancer Therapeutics–the Phase I Program, medical director, the Institute for Personalized Cancer Therapy (IPCT), the Nellie B. Connally Chair in Breast Cancer, the University of Texas MD Anderson Cancer Center, discusses the phase 2 DESTINY-PanTumor02 trial (NCT04482309) of fam-trastuzumab deruxtecan-nxki (Enhertu) in difficult-to-treat HER2-positive solid tumors.

At the 2023 ASCO Annual Meeting, investigators presented data from the phase 2 study

, specifically focusing on results from the primary end point of the trial of investigator-assessed objective response rate (ORR), Meric-Bernstam begins. Some of the secondary end points, such as duration of response (DOR) and disease control rate, were also discussed. Notably, investigators saw a response across multiple tumor types, including cervical, endometrial, ovarian, biliary tract, bladder, and other cancers, Meric-Bernstam adds.

The ORR in the total population of the 267 patients was 37.1%, including a complete response rate of 5.6%. Moreover, the overall median DOR reported was 11.8 months. In patients with cervical (n = 40), endometrial (n = 40), ovarian (n = 40), biliary tract (n = 41) pancreatic (n = 25), bladder (n = 41), and other cancers (n = 40) the ORRs were 50.0%, 57.5%, 45.0%, 22.0%, 4.0%, 39.0%, and 30.0%, respectively.

The cohort where patients experienced the least amount of activity with trastuzumab deruxtecan was pancreatic cancer, Meric-Bernstam continues. However, this was not a surprising results since pancreatic cancer is a traditionally difficult disease to treat, Meric-Bernstam says. Notably, patients in the pancreatic cancer cohort experienced a stable disease rate of 68%, Meric-Bernstam concludes.

Funda Meric-Bernstam, MD, discusses the phase 2 DESTINY-PanTumor02 trial of trastuzumab deruxtecan in difficult-to-treat HER2-positive solid tumors.


Dr Meric-Bernstam on the Use of Trastuzumab Deruxtecan in HER2+ Solid Tumors

Funda Meric-Bernstam, MD, chair of the Department of Investigational Cancer Therapeutics, medical director of the Institute for Personalized Cancer Therapy, The Nellie B. Connally Chair in Breast Cancer, and a professor, Department of Breast Surgical Oncology, Division of Surgery, at The University of Texas MD Anderson Cancer Center, discusses the safety and efficacy of the HER2-targeted bispecific antibody ZW25 in HER2-expressing solid tumors.

 amplified gastroesophageal (GEJ) cancer, biliary tract cancer, colorectal cancer (CRC), and other cancers received ZW25 at a dose of 10 mg/kg every week, or 20 mg/kg every 2 weeks. Patients received a median of 4 prior therapies. Notably, 87% of patients with GEJ cancer and 55% of patients with non-GEJ cancer received at least one prior HER2-targeted therapy, says Meric-Bernstam.

According to investigators, no new safety signals were observed. Data presented at the 2019 ESMO Congress demonstrated that the most common treatment-related adverse events were grade ≤2 diarrhea (45%) and infusion-related reactions (28%), says Meric-Bernstam. At the time of data cut-off, the partial response (PR) rate was 34.8% in 46 of 58 evaluable patients. Encouragingly, investigators reported PRs in biliary cancer, CRC, GEJ, as well as other tumor types including endometrial and ovarian cancer.

Funda Meric-Bernstam, MD, discusses the safety and efficacy of the HER2-targeted bispecific antibody ZW25 in HER2-expressing solid tumors.

Dr. Meric-Bernstam on the Safety and Efficacy of ZW25 in HER2-Expressing Solid Tumors

Funda Meric-Bernstam, MD, chair of the Department of Investigational Cancer Therapeutics, medical director of the Institute for Personalized Cancer Therapy, and a professor in the Divisions of Cancer Medicine and Surgery at The University of Texas MD Anderson Cancer Center, discusses the activity of the combination of telaglenastat (CB-839) and cabozantinib (Cabometyx) in heavily pretreated patients with metastatic renal cell carcinoma (mRCC).

Overall, the combination of telaglenastat and cabozantinib was well tolerated, says Meric-Bernstam. The recommended phase II dose of telaglenastat was 800 mg twice daily, which is the same as the recommended dose for the monotherapy. The adverse event profile was in line with what has been seen with cabozantinib alone. Notably, preliminary efficacy with the regimen was promising, she adds. Among 12 of 13 evaluable patients, 2 had papillary carcinoma. In the overall population, the objective response rate (ORR) was 42%. In the 10 patients with clear cell RCC, the ORR was 50% with the regimen.

In terms of response trends, investigators noted some deep responses in patients who were heavily pretreated. Regarding the duration of response, 5 patients received 14 months of treatment or more. At the time of data cut-off, 3 patients were still on treatment. The time to treatment response was more varied; some patients had early responses to the treatment, whereas others had delayed responses. This underscores the need for further follow-up, concludes Meric-Bernstam.

Dr. Meric-Bernstam on the Activity of Telaglenastat and Cabozantinib in mRCC

Funda Meric-Bernstam, MD, chair, Department of Investigational Cancer Therapeutics, medical director, Institute for Personalized Cancer Therapy, professor of medicine, The University of Texas MD Anderson Cancer Center, discusses preliminary data with a novel combination in renal cell carcinoma (RCC).

In a phase I study presented at the 2019 Genitourinary Cancers Symposium, the glutaminase inhibitor CB-839 was combined with the VEGF TKI cabozantinib (Cabometyx). Meric-Bernstam says that preliminary efficacy looks promising and that the combination had a similar toxicity profile to cabozantinib alone.

Of the 13 patients enrolled in the study, 12 were evaluable for response. Objective response rate (ORR) in the general population of patients with RCC was 42%. Of the 10 patients with clear-cell RCC, the ORR was 50%. Moreover, the combination led to durable responses in a heavily pretreated patient population, Meric-Bernstam adds. Five patients remained on therapy for 14 months or longer, and 3 patients remained on treatment at the time of data cut-off. Notably, some patients demonstrated delayed response, so longer-term follow-up will paint a clearer picture of the durability of these responses, says Meric-Bernstam.

Funda Meric-Bernstam, MD, chair, Department of Investigational Cancer Therapeutics, medical director, Institute for Personalized Cancer Therapy, professor of medicine, The University of Texas MD Anderson Cancer Center, discussed preliminary data with a novel combination in the treatment of patients with renal cell carcinoma.

Dr. Meric-Bernstam Discusses Novel Combination in RCC

Funda Meric-Bernstam, MD, chair, Department of Investigational Cancer Therapeutics, medical director, Institute for Personalized Cancer Therapy, professor of medicine, The University of Texas MD Anderson Cancer Center, discusses the combination of CB-839 plus cabozantinib (Cabometyx) in patients with renal cell carcinoma (RCC).

Cancer cell metabolism is increasingly becoming acknowledged as an important therapeutic target. Glutamine and glucose are key nutrients, while glutaminase converts glutamine into glutamate, enhancing its utilization. The fact that glutaminase is expressed at high levels in RCC supports the rationale for combining the glutaminase inhibitor CB-839 with a VEGF TKI. In vivo, anti-tumor activity is increased with this combination, Meric-Bernstam says.

A phase I study looking at this combination was presented at the 2019 Genitourinary Cancers Symposium. Cabozantinib was given at 60 mg per day, while CB-839 was administered twice daily at 600 mg or 800 mg. In the study of 13 patients with RCC, 11 had clear cell disease and 2 had papillary disease. Overall, the combination appeared to be well tolerated, with the recommended dose of CB-839 being 800 mg twice daily—the same as the monotherapy’s recommended dose.


Funda Meric-Bernstam, MD, chair, Department of Investigational Cancer Therapeutics, medical director, Institute for Personalized Cancer Therapy, professor of medicine, The University of Texas MD Anderson Cancer Center, discusses the combination of CB-839 plus cabozantinib in patients with renal cell carcinoma.

Funda Meric-Bernstam, MD

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